PMID- 8646519
OWN - NLM
STAT- MEDLINE
DCOM- 19960719
LR  - 20201219
IS  - 1068-9265 (Print)
IS  - 1068-9265 (Linking)
VI  - 3
IP  - 2
DP  - 1996 Mar
TI  - In situ cytokine production by breast cancer tumor-infiltrating lymphocytes.
PG  - 176-84
AB  - BACKGROUND: Human breast cancers progressively grow despite the presence of 
      extensive lymphocytic infiltration and specific antitumor immune recognition, 
      thereby calling into question the competency of breast tumor-infiltrating 
      lymphocytes (TIL). The function of breast TILs in vivo and their possible role in 
      the suppression of an antitumor immune response are largely unknown. METHODS: The 
      cytokines produced in situ by lymphocytes in 89 breast carcinomas and 14 benign 
      breast lesions were assessed using immunohistochemistry. RESULTS: The majority of 
      tumor and benign breast samples contained T-cell infiltrates, which were 
      disclosed using an anti-CD3 antibody stain. The percentage of tumor samples in 
      which > or =3% of the lymphocytes were producing cytokines was as follows: 
      interleukin (IL)-2 45%, IL-4 36%, tumor necrosis factor-alpha (TNF-alpha) 28%, 
      transforming growth factor-beta 1 (TGF-beta 1) 20%, IL-10 11%, interferon-gamma 
      (IFN-gamma) 4%, and granulocyte-macrophage colony-stimulating factor (GM-CSF) 3%. 
      Production of IL-2, IL-4, and TGF-beta 1 by TILs in breast cancers exceeded that 
      detected in benign breast lesions (p < 0.005). Significantly more tumor samples 
      contained lymphocytes producing IL-2, IL-4, TGF-beta 1, and TNF-alpha than 
      IFN-gamma and GM-CSF (p < 0.002 for each comparison). One or more of the 
      potentially immunoinhibitory cytokines-IL-4, IL-10, or TGF-beta 1-were produced 
      by lymphocytes in 44% of the specimens. No significant associations were seen 
      between lymphocyte production of a particular cytokine and disease-free survival 
      (median follow-up 43 months). CONCLUSIONS: Immunohistochemical techniques can be 
      used to detect cytokine secretion by TILs in preserved tissue. The relative lack 
      of secretion of IFN-gamma and GM-CSF, rather than a deficiency of IL-2, may 
      explain why the antitumor immune response to breast cancer is impaired.
FAU - Camp, B J
AU  - Camp BJ
AD  - Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, 
      USA.
FAU - Dyhrman, S T
AU  - Dyhrman ST
FAU - Memoli, V A
AU  - Memoli VA
FAU - Mott, L A
AU  - Mott LA
FAU - Barth, R J Jr
AU  - Barth RJ Jr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Surg Oncol
JT  - Annals of surgical oncology
JID - 9420840
RN  - 0 (Cytokines)
SB  - IM
MH  - Breast Neoplasms/*metabolism/mortality/pathology
MH  - Carcinoma, Ductal, Breast/*metabolism/mortality/pathology
MH  - Cytokines/*biosynthesis
MH  - Female
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Lymphatic Metastasis
MH  - Lymphocytes, Tumor-Infiltrating/*metabolism
MH  - Paraffin Embedding
MH  - Prognosis
MH  - Survival Rate
EDAT- 1996/03/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
AID - 10.1007/BF02305798 [doi]
PST - ppublish
SO  - Ann Surg Oncol. 1996 Mar;3(2):176-84. doi: 10.1007/BF02305798.